Synthesis and testing of a p-H2 hyperpolarized 13C probe based on the pyrazolo[1,5-a]pyrimidineacetamide DPA-713, an MRI vector to target the peripheral benzodiazepine receptors.

ABSTRACT

DPA-713 is the lead compound of a recently developed 2-phenylpyrazolo[1,5-a]pyrimidineacetamide series that has been shown to display a good targeting capability toward peripheral benzodiazepine receptors, recently renamed translocator protein (18 kDa) or in short TSPO. On the basis of this structure, a novel derivative bearing a [(13)C]butynoate moiety has been designed and synthesized (three steps-42% overall yield) providing, upon rapid and quantitative para-hydrogenation, the corresponding hyperpolarized [(13)C]alkene. Para-hydrogen-induced polarization effects have been detected in both (1)H and (13)C-NMR spectra. Upon applying a field cycling procedure, the spin order of para-H(2) added hydrogens is transferred on the (13)C carboxylate moiety yielding a signal enhancement of approximately 4500 times. T(1) of the carboxylate carbon atom is approximately 21.9 s (at 9.37 T). A (13)C-MR image has been acquired by using the (13)C RARE (Rapid Acquisition by Relaxation Enhancement) acquisition protocol on a 10-mM solution. The main limitation to the in vivo use of this novel para-hydrogenated [(13)C]derivative is its relatively low solubility in aqueous systems.